Historical Outcomes in Metastatic Renal Cell Carcinoma

Brian Rini, MD: Prognosis in metastatic kidney cancer has changed dramatically as I’ve been doing this over 2 decades. It was 12 months in the era of cytokines; it was 2-plus years in the targeted therapy era; and now it’s beyond 3 years with immunotherapies. So it’s really tripled since I’ve started. Based on a risk category, which is usually either the MSKCC [Memorial Sloan Kettering Cancer Center] risk category or IMDC. They’re both commonly used, clinical categories. There’s favorable-, intermediate-, and poor-risk patients, and they definitely have different outcomes and different prognoses. Favorable-risk patients probably have over a 4-year survival; intermediate patients probably average between 2 to 3 years; and poor-risk patients unfortunately still have about a year median survival, maybe 16 months.

The main prognostic factors in kidney cancer have historically been the Memorial Sloan Kettering risk factors. There are 5 of those risk factors. There were a few different publications. Ultimately, there are 5 risk factors, which include performance status, time from diagnosis to metastatic disease, and laboratory values, such as LDH [lactate dehydrogenase] and calcium.

Based on whether patients have or don’t have those adverse risk features, they’re categorized into 1 of 3 categories with different outcomes. Those were developed in the era of interferon, yet they still apply to targeted therapy and probably still apply to immune therapy. Not surprisingly, performance status and speed of metastatic disease is important regardless of the therapy.

IMDC is the International Metastatic Database Consortium. It’s a retrospective project that Danny Heng organized. It involves now 15 to 20 hospitals, including ours, that contribute retrospective data. This was looked at in the era of targeted therapy and developed for patients receiving targeted therapy. It includes 6 factors, including the ones I previously mentioned but also neutrophils and platelets. They’re overlapping, and most patients who are categorized as good risk in one will be good risk in the other. They’re both complimentary.

David F. McDermott, MD: Outcomes for patients with advanced kidney cancer have changed dramatically over the last 10 years. We’ve traditionally used clinical prognostic criteria to predict outcomes when patients present with metastatic disease, ranking them as either good or intermediate or poor risk based on certain clinical criteria. Over the years, survival times have improved dramatically, 50% or 100%, compared with where we were just 10 years ago. Even in a good-risk patient, the median overall survival might have been 2 years. Now, you can expect almost double that with the new therapies. Clearly, the therapies we have and the combinations we’re developing and sequencing have led to much more meaningful survival for our patients. Patients are living longer and doing better while they’re alive.

Brian Rini, MD: A current unmet need in kidney cancer is higher cure rates. We have drugs that can control disease, we have reasonably high response rates, but they’re never high enough until they’re 100%. But certainly, before immunotherapeutics, our cure rate was relatively low. With high-dose interleukin-2, it might be 5% or so. With targeted therapy, I’m not sure anybody is really cured, even if they have very long duration of disease control. With some of the new mutant therapies, especially combinations, I think we’re going to be curing a fraction of patients. I don’t know what that number will be, but I think it’s going to be in the 10%-to-20% range.

David F. McDermott, MD: There has been a major weakness of our field. We have all of these treatment options, but how do we assign a treatment in the advanced setting to a particular patient? We spent a lot of time trying to develop blood-based or tissue-based biomarkers for our patients and have struggled. We haven’t been able to come up with great markers. That may be in part because the genetic mutations that drive kidney cancer are not necessarily activating mutations as they might be for lung cancer, for example, where you can identify a particular mutation and predict, based on that mutation, what therapy to use. We’re not there. We’re not likely going to get there for patients with metastatic kidney cancer, but we are making progress. We saw that here at this ESMO [European Society for Medical Oncology] meeting for the first time, where certain markers are predictors of, for example, responsiveness to angiogenesis. An angiogenesis-high gene set has been predictive of benefit with VEGF TKIs [tyrosine kinase inhibitors] now, confirmed by the IMmotion151 study.

It’s the same thing for immune therapy and T-effector–high or CD8-positive immune-infiltrated tumors; they tend to benefit more from immune therapies, these immune checkpoint inhibitors. I think we’re making progress. We haven’t turned those insights into diagnostic tests yet, so they’re not ready for primetime as it relates to clinical decision making. But at least we have a sense that we may be able to identify who should use a VEGF strategy and who should use an immunotherapy. Now we have to work to figure out which patients should get which combination therapy.

Transcript Edited for Clarity

Transcript:

Brian Rini, MD: Prognosis in metastatic kidney cancer has changed dramatically as I’ve been doing this over 2 decades. It was 12 months in the era of cytokines; it was 2-plus years in the targeted therapy era; and now it’s beyond 3 years with immunotherapies. So it’s really tripled since I’ve started. Based on a risk category, which is usually either the MSKCC [Memorial Sloan Kettering Cancer Center] risk category or IMDC. They’re both commonly used, clinical categories. There’s favorable-, intermediate-, and poor-risk patients, and they definitely have different outcomes and different prognoses. Favorable-risk patients probably have over a 4-year survival; intermediate patients probably average between 2 to 3 years; and poor-risk patients unfortunately still have about a year median survival, maybe 16 months.

The main prognostic factors in kidney cancer have historically been the Memorial Sloan Kettering risk factors. There are 5 of those risk factors. There were a few different publications. Ultimately, there are 5 risk factors, which include performance status, time from diagnosis to metastatic disease, and laboratory values, such as LDH [lactate dehydrogenase] and calcium.

Based on whether patients have or don’t have those adverse risk features, they’re categorized into 1 of 3 categories with different outcomes. Those were developed in the era of interferon, yet they still apply to targeted therapy and probably still apply to immune therapy. Not surprisingly, performance status and speed of metastatic disease is important regardless of the therapy.

IMDC is the International Metastatic Database Consortium. It’s a retrospective project that Danny Heng organized. It involves now 15 to 20 hospitals, including ours, that contribute retrospective data. This was looked at in the era of targeted therapy and developed for patients receiving targeted therapy. It includes 6 factors, including the ones I previously mentioned but also neutrophils and platelets. They’re overlapping, and most patients who are categorized as good risk in one will be good risk in the other. They’re both complimentary.

David F. McDermott, MD: Outcomes for patients with advanced kidney cancer have changed dramatically over the last 10 years. We’ve traditionally used clinical prognostic criteria to predict outcomes when patients present with metastatic disease, ranking them as either good or intermediate or poor risk based on certain clinical criteria. Over the years, survival times have improved dramatically, 50% or 100%, compared with where we were just 10 years ago. Even in a good-risk patient, the median overall survival might have been 2 years. Now, you can expect almost double that with the new therapies. Clearly, the therapies we have and the combinations we’re developing and sequencing have led to much more meaningful survival for our patients. Patients are living longer and doing better while they’re alive.

Brian Rini, MD: A current unmet need in kidney cancer is higher cure rates. We have drugs that can control disease, we have reasonably high response rates, but they’re never high enough until they’re 100%. But certainly, before immunotherapeutics, our cure rate was relatively low. With high-dose interleukin-2, it might be 5% or so. With targeted therapy, I’m not sure anybody is really cured, even if they have very long duration of disease control. With some of the new mutant therapies, especially combinations, I think we’re going to be curing a fraction of patients. I don’t know what that number will be, but I think it’s going to be in the 10%-to-20% range.

David F. McDermott, MD: There has been a major weakness of our field. We have all of these treatment options, but how do we assign a treatment in the advanced setting to a particular patient? We spent a lot of time trying to develop blood-based or tissue-based biomarkers for our patients and have struggled. We haven’t been able to come up with great markers. That may be in part because the genetic mutations that drive kidney cancer are not necessarily activating mutations as they might be for lung cancer, for example, where you can identify a particular mutation and predict, based on that mutation, what therapy to use. We’re not there. We’re not likely going to get there for patients with metastatic kidney cancer, but we are making progress. We saw that here at this ESMO [European Society for Medical Oncology] meeting for the first time, where certain markers are predictors of, for example, responsiveness to angiogenesis. An angiogenesis-high gene set has been predictive of benefit with VEGF TKIs [tyrosine kinase inhibitors] now, confirmed by the IMmotion151 study.

It’s the same thing for immune therapy and T-effector–high or CD8-positive immune-infiltrated tumors; they tend to benefit more from immune therapies, these immune checkpoint inhibitors. I think we’re making progress. We haven’t turned those insights into diagnostic tests yet, so they’re not ready for primetime as it relates to clinical decision making. But at least we have a sense that we may be able to identify who should use a VEGF strategy and who should use an immunotherapy. Now we have to work to figure out which patients should get which combination therapy.